It has been shown that certain membrane-associated proteins require the addition of lipophilic residues in order to function properly. One family of such modifications is termed "prenylation" because the hydrophobic residue is derived from isoprenoid precursors. The prenyl residue is known to attach to the sulfhydryl group of a cysteine which has been shown in a number of membrane-associated proteins to be contained in a "CXXX" (SEQ ID NO:1) box at the carboxy terminus of the substrate protein. In particular, such membrane-associated proteins have been shown to be associated with a protein product of the ras oncogene. Summaries of these reactions conferring hydrophobic properties on membrane enzymes, including prenylation, have appeared by Hoffman, M., Science (1991) 254:650-651, and by Gibbs, J. B., Cell (1991) 65:1-4.
In the prenylation substrate proteins studied to date, the CXXX (SEQ ID NO:1) box contains aliphatic residues in the second and third positions and a leucine, serine, methionine, cysteine or alanine in the terminal position. Thus, in the CXXX (SEQ ID NO:1) boxes so far studied, the box itself is relatively hydrophobic.
It has now been found that prenylation of a viral protein is necessary for the morphogenesis of HDV virus. The viral protein which is the target of prenylation, surprisingly, contains a hydrophilic CXXX (SEQ ID NO:1) box of the sequence Cys-Arg-Pro-Gln (SEQ ID NO:2). This relatively hydrophilic CXXX (SEQ ID NO:1) box and corresponding CXXX (SEQ ID NO:1) boxes (hydrophilic or otherwise) or other cysteine-containing sequences near the C-terminus of proteins in other virions are suitable targets for antiviral strategies.